Anti-TNF are usually maintained during pregnancy in patients with inflammatory bowel disease (IBD) but safety is still a concern for them.

To provide data on management of anti-TNF agents during pregnancy, safety of live vaccines (BCG-MMR-rotavirus) and breastfeeding in newborns and dedicated information delivered to IBD women.

We performed an observational study in 25 centers from 2016 to 2018. We administered questionnaires to women with IBD receiving anti-TNF during pregnancy with newborn follow-up ≥ one year.

Of 153 patients, 52 % maintained anti-TNF during the third trimester. Anti-TNF was shortly resumed in 79 % (58/73) after delivery. The rate of breastfeeding was 44 % (68/153) without any complication; 38 % of the mothers denied to breastfeed based on physician's advice. 26 % (34/129) of the newborns received live vaccines before 6 months-old (BCG:30 %; MMR:63 %; Rotavirus:8 %) and only 3 complications occurred (local BCGitis=1, fever=2). Information concerning anti-TNF during pregnancy/post-partum was delivered to 92 % of the patients, mainly by a gastroenterologist (97 %) who discussed with the obstetrician or the paediatrician in only 48 % and 25 %.

In IBD patients, maintaining anti-TNF during pregnancy and breastfeeding is safe. Accidental live vaccines before 6 months did not lead to significant adverse events. The communication about these questions remains to improve.

Inflammatory bowel disease (IBD) has a peak age of diagnosis before the age of 35 years. Concerns about infertility, adverse pregnancy outcomes, and heritability of IBD have influenced decision-making for patients of childbearing age and their care providers. The interplay between the complex physiology in pregnancy and IBD can affect placental development, microbiome composition and responses to therapy. Current evidence has shown that effective disease management, including pre-conception counselling, multidisciplinary care and therapeutic agents to minimize disease activity, can improve pregnancy outcomes. This Review outlines the management of IBD in pregnancy and the safety of IBD therapies, including novel agents, with regard to both maternal and fetal health. The vast majority of IBD therapies can be used with low risk during pregnancy and lactation without substantial effects on neonatal outcomes.

Inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, occur worldwide and affect people of all ages, with a high impact on their quality of life. Sex differences in incidence and prevalence have been reported, and there are also gender-specific issues that physicians should recognize. For women, there are multiple, important concerns regarding issues of body image and sexuality, menstruation, contraception, fertility, pregnancy, breastfeeding and menopause. This practice-based review focuses on the main themes that run through the life of women with inflammatory bowel diseases from puberty to menopause. Gastroenterologists who specialize in inflammatory bowel diseases and other physicians who see female patients with inflammatory bowel diseases should provide support for these problems and offer adequate therapy to ensure that their patients achieve the same overall well-being and health as do women without inflammatory bowel diseases.

Patients with inflammatory bowel disease (IBD) may be at increased risk of adverse neonatal outcomes. The aim of this study was to determine pooled incidences and risk factors for these outcomes.

Medline, Embase, and Cochrane Library were searched through May 2019 for studies reporting adverse neonatal outcomes in IBD. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

The pooled incidence of preterm birth, low birth weight, congenital anomalies, and infants transferred to the neonatal intensive care unit was 8.6% (95% CI, 7.0%-10.1%), 8.9% (95% CI, 7.3%-10.5%), 2.1% (95% CI, 1.6%-2.6%), and 4.9% (95% CI, 2.9%-6.9), respectively. Compared with healthy controls, patients with IBD were more likely to deliver infants with low birth weight (<2500 grams; OR, 2.78; 95% CI, 1.16-6.66) and infants admitted to the intensive care unit (OR, 3.33; 95% CI, 1.83-6.05). Patients with Crohn's disease had an increased incidence of congenital anomalies (OR, 3.03; 95% CI, 1.43-6.42). Among IBD patients, active disease was associated with increased incidence of preterm birth (OR, 2.06; 95% CI, 1.21-3.51), low birth weight (OR, 2.96; 95% CI, 1.54-5.70), and small for gestational age (OR, 2.62; 95% CI, 1.18-5.83). Antitumor necrosis factor (anti-TNF) use during pregnancy was associated with an increased incidence of neonatal intensive care unit admission (OR, 2.42; 95% CI, 1.31-4.45) and low birth weight (OR, 1.54; 95% CI, 1.01-2.35).

Patients with IBD, particularly with active disease or requiring anti-TNF therapy, may be at increased risk of developing adverse neonatal outcomes.

Malnutrition and weight loss are common features of patients with inflammatory bowel disease (IBD).

To explore the impact of inadequate gestational weight gain (GWG) on adverse outcomes among IBD mothers in the prospective US pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) cohort.

The PIANO cohort comprises 559 and 363 pregnant mothers with Crohn's disease (CD) and ulcerative colitis (UC), respectively, enrolled between 2006 and 2014. The mothers were followed during and after pregnancy to ascertain medication, measurement of disease activity and complications during pregnancy and at delivery. Inadequate GWG was based on US Institute of Medicine recommendations. The associations between inadequate GWG and adverse pregnancy outcomes in maternal IBD were analyzed, adjusted for diabetes, hypertension, smoking, maternal age, education, and disease activity.

Maternal CD and UC with inadequate GWG had a 2.5-fold increased risk of preterm birth (OR 2.5, CI 1.3, 4.9 and OR 2.5, CI 1.2, 5.6). Furthermore, an increased risk of intrauterine growth restriction and a trend for small for gestational age were demonstrated in CD but not in UC (OR 3.3, CI 1.1, 10.0, OR 4.5, CI 0.8, 24.3, p = 0.08). Flares increased risk of inadequate GWG (OR 1.6, CI 1.2, 2.3, p = 0.002) but did not change the associations between inadequate GWG and adverse pregnancy outcomes in our models.

The US PIANO cohort demonstrated that inadequate GWG was a strong independent predictor of adverse pregnancy outcomes in IBD mothers.

Patients with inflammatory bowel disease (IBD) are in general prone to weight loss. We explored the risk of inadequate gestational weight gain (GWG), and the impact of GWG on adverse pregnancy outcomes, among mothers with IBD in the Norwegian Mother and Child Cohort Study (MoBa).

The MoBa with 95,200 mothers enrolled from 1999 to 2008, comprised 217 mothers with ulcerative colitis and 166 with Crohn's disease. Demographics were ascertained through a basic questionnaire before the first ultrasound visit and an IBD history and disease activity during pregnancy through a questionnaire mailed out in 2013. Inadequate GWG was based on the US Institute of Medicine recommendations. The associations between IBD and inadequate GWG or adverse pregnancy outcomes were explored, adjusted for diabetes, hypertension, smoking, maternal age, education, and disease activity.

Mothers with Crohn's disease (34.3%) and ulcerative colitis (26.7%) were more frequently exposed to inadequate GWG compared with non-IBD mothers (19.4%) (adjusted odds ratio [aOR] = 2.02, 95% confidence interval [CI], 1.42-2.86 and aOR = 1.46, 95% CI, 1.04-2.05, respectively). Mothers with IBD with inadequate GWG (exposed) had a 2-fold risk of small for gestational age infants compared with exposed non-IBD mothers (aOR = 1.93, 95% CI, 1.13-3.29). Exposed mothers with Crohn's disease and ulcerative colitis had a several-fold increased risk of small for gestational age compared with nonexposed IBD mothers (aOR = 4.5, 95% CI, 1.3-16.2, aOR = 5.5, 95% CI, 1.6-18.5). Disease activity was associated with reduced GWG (<13 kg compared with >17.5 kg) (aOR = 3.34, 95% CI, 1.33-8.38).

Inadequate GWG should be considered as a risk factor for adverse pregnancy outcomes or as a marker of disease activity.

The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) have been associated with an increased risk of preterm birth.

We identified all 246 singleton preterm births among women with IBD between July 2006 and December 2010 as cases and an equal number of controls with IBD from the Swedish national health registers, matched by maternal age, parity and IBD diagnosis (CD/UC). From register data and medical charts, we obtained information on reproductive history, comorbidity, disease activity and drug treatment (corticosteroids, 5-aminosalicylates, sulfasalazine, thiopurines and anti-TNF) as risk factors for preterm birth. Associations were estimated using conditional logistic regression and results were presented as odds ratios (OR) with 95% confidence intervals (CI).

Previous preterm birth was more common among cases, OR 6.13 (95%CI: 2.51-15.01). Significant activity at any time during pregnancy (OR: 2.20; 95%CI: 1.37-3.53), and in particular both in early and in late pregnancy, was more common for cases (OR: 4.78 95%; CI: 2.10-10.9). The OR for immunosuppressive treatment with thiopurines or anti-TNF was 1.88 (1.04-3.39) without significant activity and 12.78 (95%CI: 3.68-44.72) with. The risk for women who discontinued thiopurines was 6.56 (1.44-29.82).

Significant activity and immunosuppressive treatment was associated with preterm birth, particularly in women with both. The existing recommendations to aim at maintaining quiescent disease during pregnancy, even if it means continuing immunosuppressive treatment, are rational.

The management of inflammatory bowel disease (IBD) poses a particular challenge during pregnancy because the health of both the mother and the fetus must be considered.

A systematic literature search identified studies on the management of IBD during pregnancy. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach.

Consensus was reached on 29 of the 30 recommendations considered. Preconception counseling and access to specialist care are paramount in optimizing disease management. In general, women on 5-ASA, thiopurine, or anti-tumor necrosis factor (TNF) monotherapy for maintenance should continue therapy throughout pregnancy. Discontinuation of anti-TNF therapy or switching from combination therapy to monotherapy may be considered in very select low-risk patients. Women who have a mild to moderate disease flare while on optimized 5-ASA or thiopurine therapy should be managed with systemic corticosteroid or anti-TNF therapy, and those with a corticosteroid-resistant flare should start anti-TNF therapy. Endoscopy or urgent surgery should not be delayed during pregnancy if indicated. Decisions regarding cesarean delivery should be based on obstetric considerations and not the diagnosis of IBD alone, with the exception of women with active perianal Crohn's disease. With the exception of methotrexate, the use of medications for IBD should not influence the decision to breast-feed and vice versa. Live vaccinations are not recommended within the first 6 months of life in the offspring of women who were on anti-TNF therapy during pregnancy.

Optimal management of IBD before and during pregnancy is essential to achieving favorable maternal and neonatal outcomes.

Inflammatory bowel disease may place women at greater risk of adverse pregnancy outcomes.

To examine the association between inflammatory bowel disease and adverse pregnancy outcomes: preterm birth, small for gestational age (SGA) birth weight, congenital anomalies, and stillbirth.

We searched PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published from January 1980 through February 2014 and reference lists of relevant studies. We reviewed 1748 citations and identified studies evaluating outcomes of pregnancies complicated by inflammatory bowel disease. Selected studies evaluated one or more of the outcomes of interest, were in English, and gave sufficient details to perform meta-analysis. Three investigators independently reviewed articles for inclusion; discordant decisions were resolved by team review and consensus. Twenty-three studies that included 15,007 women with inflammatory bowel disease (5449 Crohn's, 6559 ulcerative colitis) and 4,614,271 controls met selection criteria. Random-effects analytical methods were used to generate pooled odds ratios.

We found an increased odds of the outcomes studied among women with inflammatory bowel disease compared with non-diseased controls: 1.85 for preterm birth (22 studies; 95 % confidence interval [CI] 1.67-2.05), 1.36 for SGA birth weight (13 studies; 95 % CI 1.16-1.60), 1.57 for stillbirth (10 studies; 95 % CI 1.03-2.38), and 1.29 for congenital anomalies (11 studies; 95 % CI 1.05-1.58). The latter result, however, may be unreliable secondary to publication bias.

Inflammatory bowel disease may increase the odds of adverse pregnancy outcomes.

Existing data on pregnancy complications in inflammatory bowel disease (IBD) are inconsistent. To address these inconsistencies, we investigated potential associations between IBD, IBD-related medication use during pregnancy, and pregnancy loss, pre-eclampsia, preterm delivery, Apgar score, and congenital abnormalities.

We conducted a cohort study in >85,000 Danish National Birth Cohort women who were pregnant in the period 1996-2002 and had information on IBD, IBD-related medication use (systemic or local corticosteroids, 5-aminosalicylates), pregnancy outcomes and potential confounders. We evaluated associations between IBD and adverse pregnancy/birth outcomes using Cox regression and log-linear binomial regression.

IBD was strongly and significantly associated with severe pre-eclampsia, preterm premature rupture of membranes and medically indicated preterm delivery in women using systemic corticosteroids during pregnancy (hazard ratios [HRs] >7). IBD was also associated with premature preterm rupture of membranes in women using local corticosteroid medications (HR 3.30, 95% confidence interval [CI] 1.33-8.20) and with medically indicated preterm delivery (HR 1.91, 95% CI 0.99-3.68) in non-medicated women. Furthermore, IBD was associated with low 5-minute Apgar score in term infants (risk ratio [RR] 2.19, 95% CI 1.03-4.66). Finally, Crohn's disease (but not ulcerative colitis) was associated with major congenital abnormalities in the offspring (RR 1.85, 95% CI 1.06-3.21). No child with a congenital abnormality born to a woman with IBD was exposed to systemic corticosteroids in utero.

Women with IBD are at increased risk of severe pre-eclampsia, medically indicated preterm delivery, preterm premature rupture of membranes, and delivering infants with low Apgar score and major congenital malformations. These associations are only partly explained by severe disease as reflected by systemic corticosteroid use.

Trying to conceive and being pregnant is an emotional period for those involved. In the majority of patients suffering from inflammatory bowel disease, maintenance therapy is required during pregnancy to control the disease, and disease control might necessitate introduction of new drugs during a vulnerable period. In this updated consensus on the reproduction and pregnancy in inflammatory bowel disease reproductive issues including fertility, the safety of drugs during pregnancy and lactation are discussed.

Individuals with Inflammatory Bowel Disease (IBD) have poor knowledge regarding the implications of disease for fertility and pregnancy. Previous studies suggest that this poor knowledge adversely influences reproductive decision making.

To examine the effect of a single group education session on IBD-specific reproductive knowledge in subjects with IBD.

People with IBD attending an educational event were invited to complete the CCPKnow questionnaire, testing reproductive knowledge in IBD, before and after an evidenced based presentation on this topic delivered by a Gastroenterologist.

Of 248 attendees, 155 participated; 69% female, mean age 40.3years. CCPKnow scores (maximum 17) were low at baseline and increased significantly post education (mean 5.4 pre vs. 14.5 post education; p<0.0001). A large majority (65.1%) of subjects had "poor" (score <8) knowledge at baseline, compared with only 1.9% after education (p<0.0001). Whilst all subareas of knowledge improved after education, the most important improvement was in attitudes toward medication use in pregnancy: 33.5% of subjects indicated at baseline that women should avoid all drugs in pregnancy compared with only 1.2% post education (p<0.0001).

A single group-delivered education event focussed on reproductive issues in IBD can dramatically improve patient knowledge. This has the potential to change reproductive behaviour and may reduce voluntary childlessness resulting from misperceptions amongst individuals with IBD.

Inflammatory bowel disease (IBD) typically affects patients during their adolescent and young adult years. As these are the reproductive years, patients and physicians often have concerns regarding the interaction between IBD, medications and surgery used to treat IBD, and reproduction, pregnancy outcomes, and neonatal outcomes. Studies have shown a lack of knowledge among both patients and physicians regarding reproductive issues in IBD. As the literature is constantly expanding regarding these very issues, with this review, we provide a comprehensive, updated overview of the literature on the management of the IBD patient from conception to delivery, and provide action tips to help guide the clinician in the management of the IBD patient during pregnancy.

IBD often affects patients during their peak reproductive years. Several drugs are available for the treatment of IBD and new drugs are continuously in the pipeline. As long-term administration of medications is often necessary, the safety of drug therapy during pregnancy and breast-feeding needs to be considered in daily clinical practice. The aim of this Review is to summarize the latest information concerning the safety of medications used to treat IBD during pregnancy and lactation, as well as their effect on fertility. Although only thalidomide and methotrexate are absolutely contraindicated during pregnancy and breast-feeding, alternatives to ciprofloxacin, natalizumab and sodium phosphate should also be considered for pregnant women. Breast-feeding is also discouraged while on treatment with ciclosporin, metronidazole and ciprofloxacin. However, therapy with 5-aminosalicylic acid preparations, glucocorticoids, thiopurines and TNF inhibitors are acceptable during pregnancy and lactation. Pregnant women who have symptomatic IBD or who require therapy should have the opportunity to discuss any associated risks to their pregnancy and infant with the appropriate consultants. By ensuring that the patient and her family are informed, the clinical outcome might be optimized.

Inflammatory bowel disease (IBD) affects a substantial number of female patients in their reproductive years. Therefore, many physicians face the dilemma whether thiopurines, prescribed to maintain remission, can be taken safely during pregnancy. Data on long-term development outcome of children exposed to maternal thiopurine therapy are very limited.

To assess the long-term effects of in utero exposure to thiopurines during pregnancy on infant health status.

A prospective multicentre follow-up study was performed in children exposed intrauterine to maternal thiopurine therapy. Physical, cognitive and social aspects of infant health status were assessed with the 43-item TNO-AZL Preschool Children Quality of Life Questionnaire (TAPQOL). Furthermore, information on visits to general practitioner and medical specialists, and physician's advice regarding lactation was evaluated. Data were compared with normative data from a control group consisting of 340 children.

Thirty children were included in this study [median 3.8 years (IQR 2.9-4.7)]. No differences on global medical and psychosocial health status were found between children exposed to intrauterine thiopurines and the reference group. Exposure to intrauterine thiopurines was not associated with increased susceptibility to infection or immunodeficiency in childhood. Twenty-one of 30 children were exclusively formula-fed based on a negative advice of medical specialists directed at thiopurine use during lactation.

Thiopurine use during pregnancy did not affect long-term development or immune function of children up to 6 years of age. Our results underscore the present notion that mothers, even those using thiopurines, should be encouraged to breastfeed their infants.

Inflammatory bowel disease (IBD) affects people during their prime reproductive years. The thiopurines (6-mercaptopurine and azathioprine), commonly used for induction and maintenance of remission, are U.S. Food and Drug Administration (FDA) pregnancy category D, raising concern for fetal risk. We performed a systematic review and meta-analysis to evaluate the effects of thiopurine exposure during pregnancy or at the time of conception on three measures of fetal risk in women and men with IBD.

A systematic search of PubMed and Web of Science using a combination of Mesh and text terms was performed to identify studies reporting birth outcomes from IBD women and men exposed to thiopurines within 3 months of conception and/or during pregnancy. A meta-analysis was performed using the random effects model to pool estimates and report odds ratio (OR) for three outcomes in women: low birth weight (LBW), preterm birth, and congenital abnormalities and one in men: congenital abnormalities.

In women with IBD exposed to thiopurines, the pooled ORs for LBW, preterm birth, and congenital abnormalities were 1.01 (95% confidence interval [CI] 0.96, 1.06), 1.67 (95% CI 1.26, 2.20), and 1.45 (95% CI 0.99, 2.13), respectively. In men, the pooled OR for congenital abnormality was 1.87 (95% CI 0.67, 5.25).

Thiopurine exposure in women with IBD was not associated with LBW or congenital abnormalities, but was associated with preterm birth. Exposure in men at the time of conception was not associated with congenital abnormalities.

Inflammatory bowel disease is a chronic disorder affecting young adults in their reproductive years, hence its populational consequences are not negligible. While fertility in inflammatory bowel disease is the same as in the general population (except for male patients with sulphasalazine treatment and females with ileum-pouch anal anastomosis), "voluntary childlessness" is higher, 14-18%. Patients require accurate counseling addressing fertility, pregnancy course and outcome. They need to be informed appropriately about risks and benefits of medications in inflammatory bowel disease in order to assist their decision making, decrease "voluntary childlessness" and improve compliance. Authors review the issues related to fertility, outcome of pregnancy, medical treatment options before and during pregnancy as well as during breastfeeding in inflammatory bowel disease.

Inflammatory bowel disease affects patients who are in their reproductive years. There are many questions regarding the management of IBD patients who are considering or who are already pregnant. These include the effect of the disease and the medications on fertility and on the pregnancy outcome.

To create an evidence-based decision-making algorithm to help guide physicians through the management of pregnancy in the IBD patient.

A literature review using phrases that include: 'inflammatory bowel disease', 'Crohn's disease', 'ulcerative colitis', 'pregnancy', 'fertility', 'breast feeding', 'delivery', 'surgery', 'immunomodulators', 'azathioprine', 'mercaptopurine', 'biologics', 'infliximab', 'adalimumab', 'certolizumab'.

The four decision-making nodes in the algorithm for the management of pregnancy in the IBD patient, and the key points for each one are as follows: (i) preconception counselling - pregnancy outcome is better if patients remain in remission during pregnancy, (ii) contemplating pregnancy or is already pregnant - drugs used to treat IBD appear to be safe during pregnancy, with the exception of methotrexate and thalidomide, (iii) delivery and (iv) breast feeding - drugs used to treat IBD appear to be safe during lactation, except for ciclosporin. Another key point is that biological agents may be continued up to 30 weeks gestation. The management of pregnancy in the IBD patient should be multi-disciplinary involving the patient and her partner, the family physician, the gastroenterologist and the obstetrician.

Inflammatory bowel disease (IBD) frequently affects women during their reproductive years. Pregnancy outcome in women with IBD is well described, particularly in retrospective studies.

To evaluate the pregnancy outcome in patients with IBD in a prospective European multicentre case-control study.

Inflammatory bowel disease pregnant women from 12 European countries were enrolled between January 2003 and December 2006 and matched (1:1) to non-IBD pregnant controls by age at conception and number of previous pregnancies. Data on pregnancy and newborn outcome, disease activity and therapy were prospectively collected every third month using a standard questionnaire. Logistic regression analysis with odds ratio was used for statistical analyses. P value<0.05 was considered significant.

A total of 332 pregnant women with IBD were included: 145 with Crohn's disease (CD) and 187 with ulcerative colitis (UC). Median age (range) at conception was 31 years (15-40) in CD and 31 (19-42) in UC patients. No statistically significant differences in frequency of abortions, preterm deliveries, caesarean sections, congenital abnormalities and birth weight were observed comparing CD and UC women with their non-IBD controls. In CD, older age was associated with congenital abnormalities and preterm delivery; smoking increased the risk of preterm delivery. For UC, older age and active disease were associated with low birth weight; while older age and combination therapy were risk factors for preterm delivery.

In this prospective case-control study, women with either Crohn's disease or ulcerative colitis have a similar pregnancy outcome when compared with a population of non-inflammatory bowel disease pregnant women.